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Comparison of Antipsychotics for Metabolic Problems in Schizophrenia or Schizoaffective Disorder

Phase 4
Completed
Conditions
Schizophrenia
Schizoaffective Disorder
Interventions
Registration Number
NCT00423878
Lead Sponsor
National Institute of Mental Health (NIMH)
Brief Summary

The study will compare the effectiveness of antipsychotic medications for patients with schizophrenia or schizoaffective disorder for whom a medication change may be indicated because of an increased risk of cardiovascular disease.

Detailed Description

Metabolic abnormalities associated with cardiovascular morbidity and premature mortality are more common in patients with schizophrenia than in matched controls. Although there is some evidence that patients with schizophrenia have intrinsic abnormalities in lipid and carbohydrate metabolism, some antipsychotics (i.e., clozapine, olanzapine, quetiapine, and risperidone) are associated with increased rates of metabolic abnormalities that predispose patients to cardiovascular disease.

This is an investigator-initiated clinical trial that will be conducted at 30 research sites that are a part of the NIMH Schizophrenia Trials Network.

The aims of the study are to (1) determine the relative effects of switching to aripiprazole, versus continued treatment with olanzapine, quetiapine, or risperidone, on metabolic parameters associated with cardiovascular disease, and (2) to determine the effects of switching to aripiprazole versus continued treatment with olanzapine, quetiapine, or risperidone on the clinical stability of schizophrenic illness.

This study design is a multi-site, single-blind (rater) randomized controlled trial of 300 patients with schizophrenia or schizoaffective disorder comparing treatment with the following medications: olanzapine, quetiapine, risperidone, and aripiprazole. The study will enroll patients with schizophrenia or schizoaffective disorder for whom a medication change may be indicated because of an increased risk of cardiovascular disease in spite of adequate control of symptoms on their current antipsychotic medication. Patients who are taking olanzapine, quetiapine, or risperidone and who have a body-mass index (BMI) greater than or equal to 27 and non-HDL cholesterol greater than or equal to 130 mg/dl will be eligible (if non-HDL is between 130-139mg/dL, LDL cholesterol must be greater than 100mg/dL). All treatments will be open label. Raters will be blinded to treatment assignment. Patients will be followed for up to 6 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
215
Inclusion Criteria
  • Diagnosed with schizophrenia or schizoaffective disorder
  • Currently treated with olanzapine, quetiapine or risperidone
  • BMI greater than or equal to 27
  • Non-HDL cholesterol greater than or equal to 130 mg/dL (if non-HDL cholesterol is between 130 - 139 mg/dL, then LDL cholesterol must be greater than 100 mg/dL).
Exclusion Criteria
  • Diabetes (FBS greater than or equal to 126) or treatment with oral hypoglycemic drug or insulin
  • Non-HDL cholesterol greater than 300 mg/dL
  • Serum triglycerides greater than 500 mg/dL
  • Patients in the first episode of schizophrenia or schizoaffective disorder
  • Known hypersensitivity to aripiprazole
  • On weight loss medications

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1AripiprazoleParticipants will switch to aripiprazole with a cross-titration from the current antipsychotic over 3-4 weeks. Allowed final dosage range for aripiprazole was 5-30 mg/day
2RisperidoneParticipants will continue with their current antipsychotic treatment, either olanzapine 5-20 mg/day, quetiapine 200-1200 mg/day, or risperidone 1-16 mg/day.
2OlanzapineParticipants will continue with their current antipsychotic treatment, either olanzapine 5-20 mg/day, quetiapine 200-1200 mg/day, or risperidone 1-16 mg/day.
2QuetiapineParticipants will continue with their current antipsychotic treatment, either olanzapine 5-20 mg/day, quetiapine 200-1200 mg/day, or risperidone 1-16 mg/day.
Primary Outcome Measures
NameTimeMethod
Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks24 weeks

Change in non-HDL cholesterol measured at baseline and every 4 weeks for 24 weeks. The efficacy analysis corresponded to a comparison of change in non-HDL cholesterol from baseline to 24 weeks between treatment groups (stay versus switch). Repeated measurements mixed effects linear models were fit for the primary analysis.

Secondary Outcome Measures
NameTimeMethod
Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C)Measured at Month 6

Trial Locations

Locations (28)

Medical College of Georgia

🇺🇸

Augusta, Georgia, United States

John C Corrigan Community Mental Health Center

🇺🇸

Fall River, Massachusetts, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

University of Massachusetts

🇺🇸

Worcester, Massachusetts, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

Mental Health Advocates

🇺🇸

Boca Raton, Florida, United States

Stanford University

🇺🇸

Palo Alto, California, United States

SHANTI Clinical Trials

🇺🇸

Colton, California, United States

Clinical Insights

🇺🇸

Glen Burnie, Maryland, United States

Washington University School of Medicine

🇺🇸

St. Louis, Missouri, United States

Lousiana State University Health Sciences Center

🇺🇸

Shreveport, Louisiana, United States

Clinical Research Institute

🇺🇸

Wichita, Kansas, United States

Freedom Trail Clinic

🇺🇸

Boston, Massachusetts, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Research Foundation for Mental Hygiene

🇺🇸

New York, New York, United States

University of Rochester

🇺🇸

Rochester, New York, United States

The University of North Carolina

🇺🇸

Chapel Hill, North Carolina, United States

John Umstead Hospital/Duke University

🇺🇸

Butner, North Carolina, United States

Philadelphia VA Medical Center-116A

🇺🇸

Philadelphia, Pennsylvania, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Carolinas HealthCare System

🇺🇸

Charlotte, North Carolina, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

New Mexico VA Healthcare System

🇺🇸

Albuquerque, New Mexico, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

University of Miami School of Medicine

🇺🇸

Miami, Florida, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

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